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Alpha-Lipoic Acid Supplementation Reduces mTORC1 Signaling in Skeletal Muscle from High Fat Fed, Obese Zucker Rats

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Lipids

Abstract

The mammalian target of rapamycin (mTOR) signaling pathway is hyperactive in liver, adipose and skeletal muscle tissues of obese rodents. Alpha-lipoic acid (αLA) has been well accepted as a weight-loss treatment, though there are limited studies on its effect on mTOR signaling in high-fat fed, obese rodents. Therefore, the goal of this study was to determine mTOR signaling and oxidative protein alterations in skeletal muscle of high-fat fed, obese rats after αLA supplementation. Phosphorylation of the mTOR substrate, eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and eIF4B were significantly reduced (p < 0.05) in muscle from αLA supplemented rats. Activation of AMP-activated protein kinase (AMPK), an mTOR inhibitory kinase, was higher (p < 0.05) in the αLA group. Protein expression of markers of oxidative metabolism, acetyl CoA carboxylase (ACC), cytochrome c oxidase IV (COX IV), peroxisome proliferator-activated receptor (PPAR), and PPAR gamma coactivator 1-alpha (PGC-1α) were significantly higher (p < 0.05) after αLA supplementation compared to non-supplemented group. Our findings show that αLA supplementation limits the negative ramifications of consuming a high fat diet on skeletal muscle markers of oxidative metabolism and mTORC1 signaling.

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Abbreviations

4E-BP1:

Eukaryotic initiation factor 4E-binding protein 1

ACC:

Acetyl CoA carboxylase

αLA:

Alpha-lipoic acid

AMPK:

AMP-activated protein kinase

COX IV:

Cytochrome c oxidase, subunit IV

CPT1:

Carnitine palmitoyltransferase I

eIF:

Eukaryotic initiation factor

HF:

High fat

mTOR:

Mammalian target of rapamycin

mTORC1:

mTOR complex 1

PGC-1α:

PPAR gamma coactivator 1-alpha

PPAR:

Peroxisome proliferator-activated receptor

rpS6:

Ribosomal protein S6

S6K1:

p70 ribosomal protein S6 kinase-1

SREBP1c:

Sterol regulatory element-binding protein 1c

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Acknowledgments

The authors would like to thank Amy Raslawsky for technical support and Dr. John Wilson for laboratory equipment use. The authors would like to thank Nutritional Fundamentals for Health for graciously donating the R+enantiomer alpha-lipoic acid (αLA) used in this study.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, SUNY, 2 Sherman Hall (Office)/5 Sherman Hall (Lab), Buffalo, NY, 14214, USA

    Zhuyun Li, Cory M. Dungan, Bradley Carrier, Todd C. Rideout & David L. Williamson

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  1. Zhuyun Li
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  2. Cory M. Dungan
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  3. Bradley Carrier
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Correspondence to David L. Williamson.

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Li, Z., Dungan, C.M., Carrier, B. et al. Alpha-Lipoic Acid Supplementation Reduces mTORC1 Signaling in Skeletal Muscle from High Fat Fed, Obese Zucker Rats. Lipids 49, 1193–1201 (2014). https://doi.org/10.1007/s11745-014-3964-x

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